This PPG proposes to use deep sequencing-based approaches to define transcriptional mechanisms that regulate inflammation and insulin resistance. An essential aspect of all three projects will be to define the consequences of gain and loss of function of regulatory proteins on global programs of macrophage and adipocyte gene expression using massively parallel RNA sequencing technologies. All three projects will also employ ChlP-Sequencing technologies to define the cistromes of wild type and mutant PPAR? and components of NCoR/SMRT co-repressor complexes. Finally, Projects 2 and 3 will use recently developed assays of three-dimensional genomic interactions (3D-DSL) to interrogate the relationship between nuclear architecture and gene expression. The PPG Deep Sequencing Core will provide two complementary services to advance these efforts; technical support for preparation and sequencing of the specific libraries required for each assay and bioinformatics/computational support to enable effective effective experimental design and utilization of the resulting data.